Association of SomaticGNAQMutation With Capillary Malformations in a Case of Choroidal Hemangioma

Abstract

IMPORTANCE Choroidal hemangiomas are defined by a thickened choroid owing to vessel overgrowth, which may increase the intraocular pressure and lead to glaucoma. Choroidal hemangioma and glaucoma often co-occur in patients with Sturge-Weber syndrome, a rare neurocutaneous disorder characterized by capillary malformations. OBJECTIVE To determine whether the mutation found in most capillary malformations, GNAQ R183Q (c.548G>A), was present in the choroidal hemangioma of a patient with Sturge-Weber syndrome. DESIGN, SETTING, AND PARTICIPANT Using laser-capture microdissection, choroidal blood vessels were isolated from paraffin-embedded tissue sections, and genomic DNA was extracted for mutational analysis. Choroidal sections were analyzed in parallel. A patient with choroidal hemangioma and Sturge-Weber syndrome who had undergone enucleation was analyzed in this study at Boston Children’s Hospital. Negative controls were choroidal tissue from an eye with retinoblastoma and unaffected lung tissue; brain tissue from a different patient with Sturge-Weber syndrome served as a positive control. Infantile hemangioma was analyzed as well. Data were analyzed in 2018. MAIN OUTCOMES AND MEASURES The mutant allelic frequency of GNAQ R183 and GNAQ Q209L/H/P was determined by droplet digital polymerase chain reaction on isolated genomic DNA. The infantile hemangioma marker glucose transporter-1 was visualized by immunofluorescent staining of tissue sections. RESULTS The GNAQ R183Q mutation was present in the patient’s choroidal vessels (21.1%) at a frequency similar to that found in brain tissue from a different patient with Sturge-Weber syndrome (25.1%). In contrast, choroidal vessels from a case of retinoblastoma were negative for the mutation (0.5%), as was lung tissue (0.2%). The patient’s choroidal tissue was negative for the 3 GNAQ mutations associated with congenital hemangioma and for the infantile hemangioma marker glucose transporter-1. CONCLUSIONS AND RELEVANCE The results suggest that a more accurate description for choroidal hemangioma in patients with Sturge-Weber syndrome is choroidal capillary malformation. This finding may explain why propranolol, used to treat infantile hemangiomas, has been largely ineffective in patients with choroidal hemangioma. Further studies are needed to corroborate this finding.

GNAQ Q209R Mutations Are Highly Specific for Circumscribed Choroidal Hemangioma

“…Tumor entities that contribute to the cluster that is dominated by variants at GNAQ p.R183 are congenital tumors/vascular malformations such as port wine stains, portwine macrocheilia and Sturge-Weber Syndrome, non-Sturge Weber capillary malformations, and diffuse choroidal hemangioma, as well as phakomatosis pigmentvascularis [13,19,20,21,22,23,26,27,28]. These malformations/tumors are diagnosed early in life, and patients often show somatic mosaicism for the variant alleles in non-neoplastic cells.…”

Circumscribed choroidal hemangioma: Clinical features and outcomes by age category in 458 cases

“…The poorer visual acuity in young patients could be a reflection of larger tumor size and greater amount of SRF or possibly related to underlying GNAQ R183Q mutation found in some of the choroidal vessels in a single published case of Sturge Weber syndrome 9 . However, differences in visual acuity and tumor size by age category remained significant even after exclusion of Sturge-Weber patients on sub-analysis, indicating that younger patients with circumscribed choroidal hemangioma have worse visual prognosis even in the absence of an associated systemic syndrome.…”

Sturge-Weber Syndrome and Haematuria: a Case Report of an Unusual Presentation

“…The GNAQ gene mutation has been described as the most likely main mutation in SWS [18]. Cells rich in GNAQ include endothelial cells in the brain, eye and skin, causing their respective disorders [19].…”